- Email: [email protected]
Comparison of histopathologic–clinical characteristics of Jessner's lymphocytic infiltration of the skin and lupus erythematosus tumidus: Multicenter study of 46 cases
Comparison of histopathologiceclinical characteristics of Jessner’s lymphocytic infiltration of the skin and lupus erythematosus tumidus: Multicenter study of 46 cases Vale´rie Re´my-Leroux, MD,a Fabienne Le´onard, MD,a Daniel Lambert, MD,b Janine Wechsler, MD,c Bernard Cribier, MD, PhD,d Pierre Thomas, MD,e Henri Adamski, MD,f Marie-Claude Marguery, MD, PhD,g Franc¸ois Aubin, MD, PhD,h Dominique Leroy, MD,i and Philippe Bernard, MD, PhDa Reims, Dijon, Cre´teil, Strasbourg, Lille, Rennes, Toulouse, Besanc¸on, and Caen, France Objective: We sought to identify criteria able to distinguish between Jessner’s lymphocytic infiltration of the skin (JLIS) and lupus erythematosus tumidus (LET). Methods: The following characteristics were recorded in a retrospective, multicenter analysis of patients with JLIS and LET: clinical features (number, size, type, and localization of lesions; photosensitivity; extracutaneous signs), histologic findings, phototesting, lupus serology, treatment, and outcome. Available histologic slides were reviewed blinded to the initial diagnosis using a pre-established grid. Results: Univariate analysis of data from patients with JLIS (15 women, 17 men; mean age: 35 years) and LET (13 women, one man; mean age: 31 years) showed the following significant (P \.05) differences: more frequent back involvement and annular lesions in JLIS, as opposed to female predominance, more frequent face involvement, and plaques in LET. Phototesting, especially ultraviolet B, induced lesions in 18 of 26 patients with JLIS and all 4 with LET. The blinded histologic review (33 samples) only found slight epidermal atrophy and focal thickened dermoepidermal junction more frequent and perivascular lymphocyte infiltrations less dense in LET. The two groups of patients reclassified according histopathologic features (18 LET and 11 JLIS) showed only slight clinical differences (more frequent nasal bridge lesions in LET and annular lesions in JLIS). Limitation: The retrospective nature of the study is a limitation. Conclusion: JLIS and LET in this population showed more similarities than differences, supporting a continuous spectrum covering these two entities. ( J Am Acad Dermatol 2008;58:217-23.)
essner’s lymphocytic infiltration of the skin (JLIS) is a cutaneous, benign disease characterized by asymptomatic erythematous papules, sometimes grouped with an arciform disposition located on the face or back, without further scarring.1-6 Histologic examination of skin lesions found
J
perivascular or periadnexal lymphocyte infiltration under a usually normal or only slight modified epidermis,1-4 although it is sometimes difficult to distinguish it from polymorphic light eruption,3,5 certain pseudolymphomas,6,7 or chronic cutaneous lupus erythematosus (CCLE),5,8-10 the latter being
From the Service de Dermatologie, Hoˆpital Robert-Debre´, Centre Hospitalier de Reimsa; Service de Dermatologie, Hoˆpital du Bocage, Centre Hospitalier de Dijonb; Service d’Anatomopathologie, Hoˆpital Henri Mondor, Centre Hospitalier de Cre´teilc; Clinique Dermatologique, Hoˆpitaux Universitaires de Strasbourgd; Clinique Dermatologique, Centre Hospitalier de Lillee; Service de Dermatologie, Hoˆpital Pontchaillou, Centre Hospitalier de Rennesf; Service de Dermatologie, Hoˆpital Purpan, Centre Hospitalier de Toulouseg; Service de Dermatologie, Hoˆpital St Jacques, Centre Hospitalier de Besanc¸onh; and Service de Dermatologie, Hoˆpital Cle´menceau, Centre Hospitalier de Caen.i
Funding sources: None. Conflicts of interest: None declared. Accepted for publication September 19, 2007. Reprints not available from the authors. Correspondence to: Philippe Bernard, MD, PhD, Centre Hospitalier de Reims, Hoˆpital Robert-Debre´, Service de Dermatologie, avenue du Ge´ne´ral Koenig, 51092 Reims Cedex, France. E-mail: [email protected]. Published online December 17, 2007. 0190-9622/$34.00 ª 2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2007.09.039
217
218 Re´my-Leroux et al
J AM ACAD DERMATOL FEBRUARY 2008
Abbreviations used: CCLE: JLIS: LET: UV:
chronic cutaneous lupus erythematosus Jessner’s lymphocytic infiltration of the skin lupus erythematosus tumidus ultraviolet
differentiated by the absence of epidermal changes, the cellular composition of its inflammatory infiltrate, and its respect of the dermoepidermal junction. Lupus erythematosus tumidus (LET) is considered to be a purely dermal form of CCLE, for which the clinical and histopathologic differential diagnosis is much more difficult. It usually presents with rounded or oval erythematous-violaceous, succulent, and well-delimited edematous lesions, located preferentially on the face or trunk.10-17 Herein, we report the results of a study comparing the clinical, histopathologic, and photobiological characteristics and outcomes of JLIS and LET in an attempt to identify diagnostic criteria able to distinguish between them.
METHODS Patients This retrospective, multicenter (n = 7) study was conducted to analyze the clinical, histologic, and photobiological characteristics of patients with JLIS or LET who had consulted during the past 15 years. For all patients included in this study, the diagnosis of JLIS or LET had been made according to the physician’s opinion, based on clinical and laboratory findings. Patients given the diagnosis of JLIS had a characteristic clinical picture as described above.1 Patients given the diagnosis of LET had single or multiple erythematous, elevated, nonscarring plaques, without any surface modification, involving the face, trunk, or both.11,15,17 Patients with cutaneous lesions suggestive clinically of discoid lupus erythematosus (ie, with scales, atrophy, or scarring) were excluded. For each patient included, routine histopathologic examination showed a dermal lymphocyte infiltration with perivascular and/or periadnexal location, under a normal or slightly atrophic epidermis, with interface changes usually absent or described as minimal. Patients with major epidermal changes histologically were excluded. The following information was collected on a questionnaire: clinical appearance of skin lesions (number, size, type, location, photosensitivity), extracutaneous signs, histopathologic reports (including direct immunofluorescence testing), phototesting results, lupus serologic workup, treatments, and outcome. For each patient, a representative histologic slide (hematoxylin-eosin) and two unstained slides, for Alcian blue staining and CD20 immunolabeling, were requested.
Photobiological examinations Photobiological examinations included evaluation of the minimal erythema dose and provocative ultraviolet (UV)B (3 minimal erythema doses on 3 consecutive days) and UVA (100 J/cm2 in a single dose, 30 J/cm2 for 3 consecutive days or, if not, total body irradiation 8-10 J/cm2 for 3 consecutive days) phototesting. The UVB phototesting was performed using a solar simulator equipped with a xenon lamp (Dermolum UM-W*, Muller, Moosinning, Germany) and UVA irradiation with a high-pressure UVA fluorescent lamp, after having stopped all treatment for at least 1 month. Tests were read at days 1 to 3, 7, and 21. Histologic re-evaluation All available histologic slides were re-examined by a group of expert dermatopathologists (B. C., D. La., and J. W.), blinded to the initial clinical diagnosis, during a single session organized expressly for this study. This evaluation first consisted of a consensual and simultaneous description of the elementary histologic lesions (quoted: absent, slight, or marked) recorded on a pre-established grid. Then a final histopathologic diagnosis (JLIS, LET, or another disease) was advanced according to unanimous consensus among experts. In a second session, Alcian blue coloration and CD20 immunolabeling were performed (J. W.) whenever unstained slides were available. Statistical analysis Univariate analyses were used to compare the different characteristics of the patients with JLIS or LET before or after histologic review. Mean ages were compared using Student t test. Percentages were compared using a Chi-square test or Fisher’s exact test for small numbers.
RESULTS Clinicalehistopathologic characteristics In all, 32 patients with JLIS and 14 with LET, according to their initial diagnoses, were included. Their main characteristics are summarized in Table I. Facial involvement, especially the nose, was more frequent in LET whereas lesions on the back were more frequent in JLIS. Annular lesions were more frequent in JLIS (Fig 1) and plaques in LET (Fig 2). Although 41 of 46 patients (89%) had a single type of lesion, 3 patients with LET and two with JLIS exhibited papules and annular lesions and/or plaques, simultaneously or successively. In both groups, no systemic involvement was observed. A positive lupus band test result, detected by direct immunofluorescence of healthy skin biopsy specimens, was inconstantly detected in patients with
Re´my-Leroux et al 219
J AM ACAD DERMATOL VOLUME 58, NUMBER 2
Table I. Main patient characteristics according to initial clinical diagnosis of Jessner’s lymphocytic infiltration of the skin or lupus erythematosus tumidus Characteristic
Patients, n Age at onset, means 6 SD, y F/M ratio, n No. of lesions, n (%) \5 \10 Location, n (%) Face Forehead Cheeks Temples Bridge of nose Back Neck, shoulders, and chest Hands Arms Other Type of lesion, n (%) Annular Plaques Papules Type of progression, n (%) Flares Photosensitivity Follow-up, y Positive lupus band test result, n (%) Antinuclear antibodies, n (%) Remission under AD, n (%)
JLIS
LET
32 14 35.2 6 4.4 31.2 6 6.2
P
NS
15/17
13/1
.003
7/30 (23) 13/30 (43)
7/13 (54) 9/13 (69)
NS NS
15/32 6/15 12/15 8/15 1/15 24/32 11/32
(47) 14/14 (100) (40) 8/14 (57) (80) 12/14 (86) (53) 4/14 (29) (7) 9/14 (64) (75) 5/14 (36) (34) 2/14 (14)
2/32 (6) 11/32 (34) 7/32 (22)
2/14 (14) 6/14 (43) 5/14 (36)
Fig 1. Typical Jessner’s lymphocytic infiltration of skin: multiple erythematous arciform lesions on back.
\.001 NS NS NS .002 .01 NS NS NS NS
14/32 (44) 1/14 (7) 3/32 (9) 11/14 (79) 21/32 (66) 6/14 (43)
.02 \.001 NS
Fig 2. Characteristic skin lesion of lupus erythematosus tumidus: single erythematous, succulent, edematous plaque on cheek.
28/32 (88) 13/14 (93) 22/32 (69) 11/14 (79) 7.5 9 0/24 (0) 5/11 (45)
NS NS
patients with JLIS and all 4 with LET; 4 patients with positive phototest results had no history of photosensitivity whereas the latter was found in 5 of 8 patients with JLIS and negative phototest results. The triggering irradiation spectrum was UVB in 12 patients (two LET, 10 JLIS), UVA in 4 patients (two with each diagnosis), and the combination of UVA and UVB in 6 patients with JLIS. High UVA doses (100 J/cm2) were more efficient to reproduce the lesions. Phototest findings became positive a mean of 6 days after the first UVB irradiation and 4.5 days after UVA, whatever the initial diagnosis. Antimalarial drugs led to an initial complete remission in 11 of 20 patients with photo-induced lesions and in 5 of 6 patients without photo-induced lesions.
.001
3/28 (11)
1/14 (7)
NS
16/24 (67)
8/10 (80)
NS
AD, Antimalarial drug; F, female; JLIS, Jessner’s lymphocytic infiltration of skin; LET, lupus erythematosus tumidus; M, male; NS, not significant.
LET. Other clinical or laboratory characteristics did not differ between the two groups (Table I). After failure of antimalarials, thalidomide was given to 4 patients with JLIS and 6 with LET: two of 3 patients with JLIS (one patient lost to follow-up) and 5 of 6 patients with LET achieved an initial complete remission. Photobiological investigations In all, 26 patients with JLIS and 4 with LET underwent provocative phototesting. Minimal erythema doses were normal for all these patients, with papular lesions induced on healthy skin in 18 of 26
Histologic review The histologic slides of 33 patients (23 JLIS and 10 LET) were available for re-evaluation. The histopathologic characteristics retained after this review are listed in Table II, according to the initial diagnoses. Only slight epidermal atrophy and focal thickening of the dermoepidermal junction were found more frequent in patients initially classified as having LET. A continuous dermoepidermal thickening was seen in only one patient (with LET). Perivascular
220 Re´my-Leroux et al
J AM ACAD DERMATOL FEBRUARY 2008
Table II. Grid of histopathologic elements used by experts during review session and comparison of patients according to initial clinical diagnoses Patients, n Epidermal atrophy Slight Marked Follicular plugging Parakeratosis* Basal keratinocyte necrosisy Epidermal vacuolization Discontinuous Continuous Thickened DEJ Focal [2/3 of DEJ Exocytotic loci Epidermal Pilar Lymphocyte-infiltrate density: Superficial dermis: Moderate or dense Intermediate and reticular dermis: Moderate Dense Lymphocyte-infiltrate location: Periadnexal (moderate or dense) Perivascular: Moderate Dense Interstitial (moderate) Bandlike (moderate or dense) Dermal edema (moderate or dense) Mucin deposits (moderate or dense) CD20 immunolabelingz Final histologic diagnosis§ JLIS LET Other No consensus
Clinical group of JLIS
Clinical group of LET
23
10
2/23 (9) 0 0 3/23 (13) 1/23 (4)
6/10 (60) 0 1/10 (10) 0 0
.004 NS NS NS NS
8/23 (35) 4/23 (17)
5/10 (50) 2/10 (20)
NS NS
3/23 (13) 0
5/10 (50) 1/10 (10)
.04 NS
11/23 (48) 11/21 (52)
4/10 (40) 7/8 (88)
NS NS
23/23 (100)
8/10 (80)
NS
10/23 (43) 13/23 (57)
2/10 (20) 8/10 (80)
NS
19/23 (83)
9/10 (90)
NS
6/23 17/23 3/23 3/23 18/23 12/23 11/21
7/10 3/10 1/10 2/10 8/10 5/10 5/9
.03
(26) (74) (13) (13) (78) (52) (52)
11 9 3 0
(70) (30) (10) (20) (80) (50) (56)
P
NS NS NS NS NS
0 9 0 1
Values are expressed as n (%) unless otherwise indicated. DEJ, Dermopidermal junction; JLIS, Jessner’s lymphocytic infiltration of skin; LET, lupus erythematosus tumidus; NS, not significant. *[1 Focus/slide. y [2 Foci/slide. z Considered as positive when number of labeled cells was [2/field (3250). § Diagnoses made without Alcian blue staining and CD20 immunolabeling results.
lymphocyte infiltrates were always less dense in LET (Figs 3 to 6). When present, epidermal vacuolization was mild and discontinued. Mucin deposits and CD201 cells were seen in half of the patients of both groups. Consensual histologic diagnoses were given by the experts (Table II). Among the 23 patients initially considered to have JLIS, 9 were reclassified as having LET because of mild epidermal changes (Table II) and 3 as other diseases (erythema annulare centrifugum, seborrheic dermatitis,
nonspecific inflammatory dermatosis); 9 of 10 patients initially given the diagnosis of LET were confirmed histologically (no consensual diagnosis could be given in the remaining patient). The characteristics of the patients initially were again compared, this time according to the consensual diagnoses (Table III). After this reclassification, the only clinical differences that still persisted were: more frequent lesions located on the nose in LET and more frequent annular lesions in JLIS. Finally,
J AM ACAD DERMATOL
Re´my-Leroux et al 221
VOLUME 58, NUMBER 2
Fig 3. Histopathologic features of lupus erythematosus tumidus: mild epidermal atrophy and perivascular lymphocyte infiltration less dense as compared with Jessner’s lymphocytic infiltration of skin. (Hematoxylin-eosin stain; original magnification: 3100.)
Fig 5. Histopathologic features of Jessner’s lymphocytic infiltration of skin: dense perivascular lymphocyte infiltration. (Hematoxylin-eosin stain; original magnification: 3100.)
Fig 4. Histopathologic features of lupus erythematosus tumidus: mild thickening of dermoepidermal junction and focal vacuolization of basal keratinocytes. (Hematoxylineosin stain; original magnification: 3250.)
Fig 6. Histopathologic features of Jessner’s lymphocytic infiltration of skin: absence of epidermal and dermoepidermal junction abnormalities. (Hematoxylin-eosin stain; original magnification: 3250.)
histologic characteristics of the two groups obtained after histologic reclassification were compared again: only a slight epidermal atrophy was found more frequent in patients with LET (Table III).
reclassification, the extent to which JLIS and LET share numerous characteristics is striking, especially for age at onset, photosensitivity, response to antimalarial drugs, lack of extracutaneous involvement, and histologic findings (CD20 expression, presence of mucin). Interestingly, photosensitivity was most frequent at the beginning of the disease and disappeared over time, with progression occurring independently of photoexposure. According to Kuhn et al,17 the single presence of even slight epidermal or junctional histologic changes should exclude the tumid subset of LE. However, in a recent report by Vieira et al,16 minimal epidermal changes (atrophy, slight vacuolar degeneration of basal cells, slight to moderate hyperkeratosis and follicular plugging) were found in 18/26 LET cases and irregular basement membrane in 11/26. Similarly, Alexiades-Armenakas et al15 noticed focal dermoepidermal interface changes with vacuolar alterations and necrosis of keratinocytes in 3 of their 15 patients with LET. In our study, after
DISCUSSION The results of this study showed that JLIS and LET have more similarities than differences. Indeed, the differential diagnosis between them seems to rely on several particularities: clinical, ie, facial lesions, especially on the nose for women with LET, and annular lesions predominantly on the back for JLIS; and immunopathologic, ie, a positive lupus band test result for LET; none of which are specific. In our series, the rarity of high-titer antinuclear antibodies in either group, the absence of positive lupus band test results in JLIS, and their irregular positivity in LET are in accordance with the literature.2,3,13,16-18 After reclassification of patients based on blinded histologic review, the clinical differences were almost totally erased. However, before or after the
222 Re´my-Leroux et al
J AM ACAD DERMATOL FEBRUARY 2008
Table III. Comparison of patient characteristics after slide review and reclassification Diagnosis after histologic review
Patients, n Age at onset, means 6 SD, y F/M ratio No. of lesions, n (%) \5 [10 Location, n (%) Face Forehead Cheeks Temples Bridge of nose Back Neck, shoulders, and chest Hands Arms Other Type of lesion, n (%) Annular Plaques Papules Type of progression, n (%) Flares Photosensitivity Positive lupus band test result, n (%) Antinuclear antibodies, n (%) Epidermal atrophy Slight Marked Epidermal vacuolization Discontinuous Continuous Thickened DEJ Focal [2/3 of DEJ Lymphocyte-infiltrate location: Periadnexal (moderate or dense) Perivascular: Moderate Dense
JLIS
LET
P
11 18 29.9 6 6.7 34.4 6 6.7 NS 6/5
12/6
NS
2/10 (20) 5/10 (50)
8/17 (47) 9/17 (53)
NS NS
7/11 (64) 2/5 (40) 5/5 (100) 4/5 (80) 0/7 9/11 (82) 5/11 (45) 1/11 (9) 5/11 (45) 3/11 (27)
13/18 8/13 12/13 4/13 7/13 9/18 4/18 3/18 6/18 5/18
(72) (62) (92) (31) (54) (50) (22) (17) (33) (28)
NS NS NS NS .04 NS NS NS NS NS
6/11 (55) 3/18 (17) 2/11 (18) 9/18 (50) 7/11 (64) 10/18 (56)
.05 NS NS
10/11 (91) 17/18 (94) 11/11 (100) 14/18 (78) 0 1/14 (7)
NS NS NS
3/10 (30)
1/17 (6)
NS
1/11 (9) 0
7/18 (39) 0
.04 NS
4/11 (36) 0
8/18 (45) 6/18 (34)
NS NS
1/11 (9) 0
6/18 (33,5) NS 1/18 (5,5) NS
10/11 (91) 16/18 (89)
NS
11/11 (100) 18/18 (100) NS 2/11 (18) 11/18 (61) .05 9/11 (82) 7/18 (39)
DEJ, Dermopidermal junction; F, female; JLIS, Jessner’s lymphocytic infiltration of skin; LET, lupus erythematosus tumidus; M, male; NS, not significant.
histologic reclassification, only a slight epidermal atrophy histologic persisted as a potential histologic criterion for separating the two conditions. Thus, although a difference between two clinical pictures seems to have been accepted in the minds of
physicians, our findings support a broader but single histopathologiceclinical spectrum rather than two distinct entities. LET is considered a rare subtype of CCLE,14,16,19-21 which differs clinically from discoid subtype by the absence of follicular hyperkeratosis and scarring.15,22 Histologically, abundant interstitial mucin deposits have been reported in skin biopsy specimens from patients with LET,14-17 but not with JLIS.1 In our series, mucin deposits were detected in about 50% of the patients who were clinically given the diagnosis of either disease. Previous studies by Konttinen et al,23 Willemze et al,8 and Rijlaarsdam et al24 showed that the infiltrates in JLIS and CCLE were mainly composed of CD41 T cells whereas Cerio et al7 observed B and T lymphocytes in more than 50% of infiltrates of patients with JLIS (the remaining 50% had no Tcell component). Our data confirmed the presence of B lymphocytes in the dermal infiltrates of more than 50% of patients initially given the diagnosis of JLIS or LET. In both conditions, these CD201 cells were generally sparse and diffusely distributed, with a range of 2 to 30 positive cells per field (3250). The notion of photosensitivity in JLIS was raised early5,25 and was shown by Toonstra et al3 to occur in 24% of cases. More recently, Weber et al,26 described 10 cases of photo-induced JLIS, with appearance of the lesions delayed 3 to 6 days after exposure, with combined UVA and UVB triggering spectra for most patients, as confirmed further by our group.27 In addition, Kuhn et al28,29 showed that LET represents the most photosensitive subtype of lupus erythematosus. These findings and our current results confirm that both JLIS and LET belong to the spectrum of photodermatoses, although the association of sun exposure and lesions is sometimes neglected because of the long delay before their appearance. Phototesting may contribute to the differential diagnosis of other photodermatoses, such as polymorphous light eruption, but contribute nothing to the differential diagnosis between JLIS and LET. Because of the absence of strict relationship between their efficacy and the existence of photoinduction of the skin lesions, antimalarial drugs may be used as firstline therapy, even in the absence of photosensitivity, as we did for our 26 patients with JLIS or LET. Notably, thalidomide, the only treatment that has been evaluated in a randomized controlled trial in JLIS,30 was given to only 10 of our patients and never as first-line therapy. After a mean of 8 years of follow-up, no systemic involvement has been reported for any of our patients with JLIS or LET, as previously reported.14,16 Rare and debatable cases of LET that evolved toward systemic lupus have been reported, but always in
J AM ACAD DERMATOL
Re´my-Leroux et al 223
VOLUME 58, NUMBER 2
patients with simultaneous discoid lupus erythematosus12,13,15 whereas that association is not exceptional.10,12-14,21 The association of JLIS and discoid lupus erythematosus is more uncommon, probably because the presence of discoid-type lesions, in principle, excludes the diagnosis of JLIS.3,31 Indeed, the current study strongly favors the hypothesis of a continuous spectrum covering JLIS and LET, most of the cases corresponding to a predominantly or purely dermal form of CCLE.32 The authors wish to thank Drs Algros, Barneon, Cotten, Durlach, Lamant, Le Gall, Petrella, Picot, and Pinquier, and Prof Pluot for providing histopathologic slides; Drs Bonnevalle and Bouthors for their help in data collection; and Mrs J. Jacobson for editorial assistance. REFERENCES 1. Jessner M, Kanof NB. Lymphocytic infiltration of the skin. Arch Dermatol 1953;68:447-9. 2. Konttinen YT, Bergroth V, Johansson E, Nordstrom D, Malmstrom M. A long-term clinicopathologic survey of patients with Jessner’s lymphocytic infiltration of the skin. J Invest Dermatol 1987;89:205-8. 3. Toonstra J, Wildschut A, Boer J, Smeenk G, Willemze R, van der Putte SC, et al. Jessner’s lymphocytic infiltration of the skin: a clinical study of 100 patients. Arch Dermatol 1989;125:1525-30. 4. Toonstra J, van der Putte SC. Plasmacytoid monocytes in Jessner’s lymphocytic infiltration of the skin: a valuable clue for the diagnosis. Am J Dermatopathol 1991;13:321-8. 5. Gottlieb B, Winkelmann RK. Lymphocytic infiltration of the skin. Arch Dermatol 1962;86:626-33. 6. Calnan CD. Lymphocytic infiltration of the skin (Jessner). Br J Dermatol 1957;69:169-73. 7. Cerio R, Oliver GF, Jones EW, Winkelmann RK. The heterogeneity of Jessner’s lymphocytic infiltration of the skin: immunohistochemical studies suggesting one form of perivascular lymphocytoma. J Am Acad Dermatol 1990;23:63-7. 8. Willemze R, Vermeer BJ, Meijer CJ. Immunohistochemical studies in lymphocytic infiltration of the skin (Jessner) and discoid lupus erythematosus: a comparative study. J Am Acad Dermatol 1984;11:832-40. 9. Weyers W, Bonczkowitz M, Weyers I. LE or not LEethat is the question: an unsuccessful attempt to separate lymphocytic infiltration from the spectrum of discoid lupus erythematosus. Am J Dermatopathol 1998;20:225-32. 10. Dekle CL, Mannes KD, Davis LS, Sangueza OP. Lupus tumidus. J Am Acad Dermatol 1999;41:250-3. 11. Gougerot H, Burnier R. Lupus erythematodes ‘‘tumidus’’. Bull Soc Fr Dermatol Syph 1930;37:1291-2. 12. Ruiz H, Sanchez JL. Tumid lupus erythematosus. Am J Dermatopathol 1999;21:356-60. 13. Choonhakarn C, Poonsriaram A, Chaivoramukul J. Lupus erythematosus tumidus. Int J Dermatol 2004;43:815-8. 14. Kuhn A, Richter-Hintz D, Oslislo C, Ruzicka T, Megahed M, Lehmann P. Lupus erythematosus tumidusea neglected subset of cutaneous lupus erythematosus: report of 40 cases. Arch Dermatol 2000;136:1033-41.
15. Alexiades-Armenakas MR, Baldassano M, Bince B, Werth V, Bystryn JC, Kamino H, et al. Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis. Arthritis Rheum 2003;49:494-500. 16. Vieira V, Del Pozo J, Yebra-Pimentel MT, Martinez W, Fonseca E. Lupus erythematosus tumidus: a series of 26 cases. Int J Dermatol 2006;45:512-7. 17. Kuhn A, Sonntag M, Ruzicka T, Lehmann P, Megahed M. Histopathologic findings in lupus erythematosus tumidus: review of 80 patients. J Am Acad Dermatol 2003;48:901-8. 18. Ten Have-Opbroek AAW. On the differential diagnosis between chronic discoid lupus erythematodes and lymphocytic infiltration of the skin (Jessner), with emphasis on fluorescence microscopy. Dermatologica 1966;132:109-14. 19. Gougerot H, Burnier R. Lupus e´rythe´mateux tumidus. Bull Soc Fr Dermatol Syph 1931;38:195. 20. Gougerot H, Carteaud A. Lupus e´rythe´mateux tumidus. Bull Soc Fr Dermatol Syph 1931;38:195-6. 21. Casala AM, Bianchi C, Bianchi O, Stringa SG. Lupus e´rythe´mateux tumidus (lymphocytic infiltration of the skin) et lupus e´rythe´mateux chronique associe´s chez le meˆme malade. Etude immunofluorescente. Bull Soc Fr Dermatol Syph 1971;78: 256-8. 22. France`s C, Barete S, Ayoub N, Piette J. Classification des le´sions dermatologiques du lupus. Ann Med Interne (Paris) 2003; 154:33-44. 23. Konttinen YT, Reitamo S, Ranki A, Segerberg-Konttinen M. T lymphocytes and mononuclear phagocytes in the skin infiltrate of systemic and discoid lupus erythematosus and Jessner’s lymphocytic infiltrate. Br J Dermatol 1981;104:141-5. 24. Rijlaarsdam JU, Nieboer C, De Vries E, Willemze R. Characterization of the dermal infiltrates in Jessner’s lymphocytic infiltrate of the skin, polymorphous light eruption and cutaneous lupus erythematosus: differential diagnostic and pathogenetic aspects. J Cutan Pathol 1990;17:2-8. 25. Krieger BL. Lymphocytic infiltration of the skin (Jessner). Arch Dermatol 1969;100:247-8. 26. Weber F, Schmuth M, Fritsch P, Sepp N. Lymphocytic infiltration of the skin is a photosensitive variant of lupus erythematosus: evidence by phototesting. Br J Dermatol 2001; 144:292-6. 27. Adamski H, Labrousse AL, Sparsa A, Leonard F, Le Gall F, Labrousse F, et al. Photode´clenchement des le´sions dans la maladie de Jessner-Kanof. Ann Dermatol Venereol 2002;129:1370-3. 28. Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, Megahed M, Ruzicka T, et al. Phototesting in lupus erythematosus: a 15year experience. J Am Acad Dermatol 2001;45:86-95. 29. Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, Megahed M, Ruzicka T, et al. Phototesting in lupus erythematosus tumidusereview of 60 patients. Photochem Photobiol 2001;73:532-6. 30. Guillaume JC, Moulin G, Dieng MT, Poli F, Morel P, Souteyrand P, et al. Crossover study of thalidomide vs placebo in Jessner’s lymphocytic infiltration of the skin. Arch Dermatol 1995; 131:1032-5. 31. Lipsker D, Mitschler A, Grosshans E, Cribier B. Could Jessner’s lymphocytic infiltrate of the skin be a dermal variant of lupus erythematosus? An analysis of 210 cases. Dermatology 2006;213:15-22. 32. Lipsker D. Classification of specific cutaneous manifestations in patients with lupus erythematosus: a time for change? Dermatology 2006;212:324-6.
essner’s lymphocytic infiltration of the skin (JLIS) is a cutaneous, benign disease characterized by asymptomatic erythematous papules, sometimes grouped with an arciform disposition located on the face or back, without further scarring.1-6 Histologic examination of skin lesions found
J
perivascular or periadnexal lymphocyte infiltration under a usually normal or only slight modified epidermis,1-4 although it is sometimes difficult to distinguish it from polymorphic light eruption,3,5 certain pseudolymphomas,6,7 or chronic cutaneous lupus erythematosus (CCLE),5,8-10 the latter being
From the Service de Dermatologie, Hoˆpital Robert-Debre´, Centre Hospitalier de Reimsa; Service de Dermatologie, Hoˆpital du Bocage, Centre Hospitalier de Dijonb; Service d’Anatomopathologie, Hoˆpital Henri Mondor, Centre Hospitalier de Cre´teilc; Clinique Dermatologique, Hoˆpitaux Universitaires de Strasbourgd; Clinique Dermatologique, Centre Hospitalier de Lillee; Service de Dermatologie, Hoˆpital Pontchaillou, Centre Hospitalier de Rennesf; Service de Dermatologie, Hoˆpital Purpan, Centre Hospitalier de Toulouseg; Service de Dermatologie, Hoˆpital St Jacques, Centre Hospitalier de Besanc¸onh; and Service de Dermatologie, Hoˆpital Cle´menceau, Centre Hospitalier de Caen.i
Funding sources: None. Conflicts of interest: None declared. Accepted for publication September 19, 2007. Reprints not available from the authors. Correspondence to: Philippe Bernard, MD, PhD, Centre Hospitalier de Reims, Hoˆpital Robert-Debre´, Service de Dermatologie, avenue du Ge´ne´ral Koenig, 51092 Reims Cedex, France. E-mail: [email protected]. Published online December 17, 2007. 0190-9622/$34.00 ª 2008 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2007.09.039
217
218 Re´my-Leroux et al
J AM ACAD DERMATOL FEBRUARY 2008
Abbreviations used: CCLE: JLIS: LET: UV:
chronic cutaneous lupus erythematosus Jessner’s lymphocytic infiltration of the skin lupus erythematosus tumidus ultraviolet
differentiated by the absence of epidermal changes, the cellular composition of its inflammatory infiltrate, and its respect of the dermoepidermal junction. Lupus erythematosus tumidus (LET) is considered to be a purely dermal form of CCLE, for which the clinical and histopathologic differential diagnosis is much more difficult. It usually presents with rounded or oval erythematous-violaceous, succulent, and well-delimited edematous lesions, located preferentially on the face or trunk.10-17 Herein, we report the results of a study comparing the clinical, histopathologic, and photobiological characteristics and outcomes of JLIS and LET in an attempt to identify diagnostic criteria able to distinguish between them.
METHODS Patients This retrospective, multicenter (n = 7) study was conducted to analyze the clinical, histologic, and photobiological characteristics of patients with JLIS or LET who had consulted during the past 15 years. For all patients included in this study, the diagnosis of JLIS or LET had been made according to the physician’s opinion, based on clinical and laboratory findings. Patients given the diagnosis of JLIS had a characteristic clinical picture as described above.1 Patients given the diagnosis of LET had single or multiple erythematous, elevated, nonscarring plaques, without any surface modification, involving the face, trunk, or both.11,15,17 Patients with cutaneous lesions suggestive clinically of discoid lupus erythematosus (ie, with scales, atrophy, or scarring) were excluded. For each patient included, routine histopathologic examination showed a dermal lymphocyte infiltration with perivascular and/or periadnexal location, under a normal or slightly atrophic epidermis, with interface changes usually absent or described as minimal. Patients with major epidermal changes histologically were excluded. The following information was collected on a questionnaire: clinical appearance of skin lesions (number, size, type, location, photosensitivity), extracutaneous signs, histopathologic reports (including direct immunofluorescence testing), phototesting results, lupus serologic workup, treatments, and outcome. For each patient, a representative histologic slide (hematoxylin-eosin) and two unstained slides, for Alcian blue staining and CD20 immunolabeling, were requested.
Photobiological examinations Photobiological examinations included evaluation of the minimal erythema dose and provocative ultraviolet (UV)B (3 minimal erythema doses on 3 consecutive days) and UVA (100 J/cm2 in a single dose, 30 J/cm2 for 3 consecutive days or, if not, total body irradiation 8-10 J/cm2 for 3 consecutive days) phototesting. The UVB phototesting was performed using a solar simulator equipped with a xenon lamp (Dermolum UM-W*, Muller, Moosinning, Germany) and UVA irradiation with a high-pressure UVA fluorescent lamp, after having stopped all treatment for at least 1 month. Tests were read at days 1 to 3, 7, and 21. Histologic re-evaluation All available histologic slides were re-examined by a group of expert dermatopathologists (B. C., D. La., and J. W.), blinded to the initial clinical diagnosis, during a single session organized expressly for this study. This evaluation first consisted of a consensual and simultaneous description of the elementary histologic lesions (quoted: absent, slight, or marked) recorded on a pre-established grid. Then a final histopathologic diagnosis (JLIS, LET, or another disease) was advanced according to unanimous consensus among experts. In a second session, Alcian blue coloration and CD20 immunolabeling were performed (J. W.) whenever unstained slides were available. Statistical analysis Univariate analyses were used to compare the different characteristics of the patients with JLIS or LET before or after histologic review. Mean ages were compared using Student t test. Percentages were compared using a Chi-square test or Fisher’s exact test for small numbers.
RESULTS Clinicalehistopathologic characteristics In all, 32 patients with JLIS and 14 with LET, according to their initial diagnoses, were included. Their main characteristics are summarized in Table I. Facial involvement, especially the nose, was more frequent in LET whereas lesions on the back were more frequent in JLIS. Annular lesions were more frequent in JLIS (Fig 1) and plaques in LET (Fig 2). Although 41 of 46 patients (89%) had a single type of lesion, 3 patients with LET and two with JLIS exhibited papules and annular lesions and/or plaques, simultaneously or successively. In both groups, no systemic involvement was observed. A positive lupus band test result, detected by direct immunofluorescence of healthy skin biopsy specimens, was inconstantly detected in patients with
Re´my-Leroux et al 219
J AM ACAD DERMATOL VOLUME 58, NUMBER 2
Table I. Main patient characteristics according to initial clinical diagnosis of Jessner’s lymphocytic infiltration of the skin or lupus erythematosus tumidus Characteristic
Patients, n Age at onset, means 6 SD, y F/M ratio, n No. of lesions, n (%) \5 \10 Location, n (%) Face Forehead Cheeks Temples Bridge of nose Back Neck, shoulders, and chest Hands Arms Other Type of lesion, n (%) Annular Plaques Papules Type of progression, n (%) Flares Photosensitivity Follow-up, y Positive lupus band test result, n (%) Antinuclear antibodies, n (%) Remission under AD, n (%)
JLIS
LET
32 14 35.2 6 4.4 31.2 6 6.2
P
NS
15/17
13/1
.003
7/30 (23) 13/30 (43)
7/13 (54) 9/13 (69)
NS NS
15/32 6/15 12/15 8/15 1/15 24/32 11/32
(47) 14/14 (100) (40) 8/14 (57) (80) 12/14 (86) (53) 4/14 (29) (7) 9/14 (64) (75) 5/14 (36) (34) 2/14 (14)
2/32 (6) 11/32 (34) 7/32 (22)
2/14 (14) 6/14 (43) 5/14 (36)
Fig 1. Typical Jessner’s lymphocytic infiltration of skin: multiple erythematous arciform lesions on back.
\.001 NS NS NS .002 .01 NS NS NS NS
14/32 (44) 1/14 (7) 3/32 (9) 11/14 (79) 21/32 (66) 6/14 (43)
.02 \.001 NS
Fig 2. Characteristic skin lesion of lupus erythematosus tumidus: single erythematous, succulent, edematous plaque on cheek.
28/32 (88) 13/14 (93) 22/32 (69) 11/14 (79) 7.5 9 0/24 (0) 5/11 (45)
NS NS
patients with JLIS and all 4 with LET; 4 patients with positive phototest results had no history of photosensitivity whereas the latter was found in 5 of 8 patients with JLIS and negative phototest results. The triggering irradiation spectrum was UVB in 12 patients (two LET, 10 JLIS), UVA in 4 patients (two with each diagnosis), and the combination of UVA and UVB in 6 patients with JLIS. High UVA doses (100 J/cm2) were more efficient to reproduce the lesions. Phototest findings became positive a mean of 6 days after the first UVB irradiation and 4.5 days after UVA, whatever the initial diagnosis. Antimalarial drugs led to an initial complete remission in 11 of 20 patients with photo-induced lesions and in 5 of 6 patients without photo-induced lesions.
.001
3/28 (11)
1/14 (7)
NS
16/24 (67)
8/10 (80)
NS
AD, Antimalarial drug; F, female; JLIS, Jessner’s lymphocytic infiltration of skin; LET, lupus erythematosus tumidus; M, male; NS, not significant.
LET. Other clinical or laboratory characteristics did not differ between the two groups (Table I). After failure of antimalarials, thalidomide was given to 4 patients with JLIS and 6 with LET: two of 3 patients with JLIS (one patient lost to follow-up) and 5 of 6 patients with LET achieved an initial complete remission. Photobiological investigations In all, 26 patients with JLIS and 4 with LET underwent provocative phototesting. Minimal erythema doses were normal for all these patients, with papular lesions induced on healthy skin in 18 of 26
Histologic review The histologic slides of 33 patients (23 JLIS and 10 LET) were available for re-evaluation. The histopathologic characteristics retained after this review are listed in Table II, according to the initial diagnoses. Only slight epidermal atrophy and focal thickening of the dermoepidermal junction were found more frequent in patients initially classified as having LET. A continuous dermoepidermal thickening was seen in only one patient (with LET). Perivascular
220 Re´my-Leroux et al
J AM ACAD DERMATOL FEBRUARY 2008
Table II. Grid of histopathologic elements used by experts during review session and comparison of patients according to initial clinical diagnoses Patients, n Epidermal atrophy Slight Marked Follicular plugging Parakeratosis* Basal keratinocyte necrosisy Epidermal vacuolization Discontinuous Continuous Thickened DEJ Focal [2/3 of DEJ Exocytotic loci Epidermal Pilar Lymphocyte-infiltrate density: Superficial dermis: Moderate or dense Intermediate and reticular dermis: Moderate Dense Lymphocyte-infiltrate location: Periadnexal (moderate or dense) Perivascular: Moderate Dense Interstitial (moderate) Bandlike (moderate or dense) Dermal edema (moderate or dense) Mucin deposits (moderate or dense) CD20 immunolabelingz Final histologic diagnosis§ JLIS LET Other No consensus
Clinical group of JLIS
Clinical group of LET
23
10
2/23 (9) 0 0 3/23 (13) 1/23 (4)
6/10 (60) 0 1/10 (10) 0 0
.004 NS NS NS NS
8/23 (35) 4/23 (17)
5/10 (50) 2/10 (20)
NS NS
3/23 (13) 0
5/10 (50) 1/10 (10)
.04 NS
11/23 (48) 11/21 (52)
4/10 (40) 7/8 (88)
NS NS
23/23 (100)
8/10 (80)
NS
10/23 (43) 13/23 (57)
2/10 (20) 8/10 (80)
NS
19/23 (83)
9/10 (90)
NS
6/23 17/23 3/23 3/23 18/23 12/23 11/21
7/10 3/10 1/10 2/10 8/10 5/10 5/9
.03
(26) (74) (13) (13) (78) (52) (52)
11 9 3 0
(70) (30) (10) (20) (80) (50) (56)
P
NS NS NS NS NS
0 9 0 1
Values are expressed as n (%) unless otherwise indicated. DEJ, Dermopidermal junction; JLIS, Jessner’s lymphocytic infiltration of skin; LET, lupus erythematosus tumidus; NS, not significant. *[1 Focus/slide. y [2 Foci/slide. z Considered as positive when number of labeled cells was [2/field (3250). § Diagnoses made without Alcian blue staining and CD20 immunolabeling results.
lymphocyte infiltrates were always less dense in LET (Figs 3 to 6). When present, epidermal vacuolization was mild and discontinued. Mucin deposits and CD201 cells were seen in half of the patients of both groups. Consensual histologic diagnoses were given by the experts (Table II). Among the 23 patients initially considered to have JLIS, 9 were reclassified as having LET because of mild epidermal changes (Table II) and 3 as other diseases (erythema annulare centrifugum, seborrheic dermatitis,
nonspecific inflammatory dermatosis); 9 of 10 patients initially given the diagnosis of LET were confirmed histologically (no consensual diagnosis could be given in the remaining patient). The characteristics of the patients initially were again compared, this time according to the consensual diagnoses (Table III). After this reclassification, the only clinical differences that still persisted were: more frequent lesions located on the nose in LET and more frequent annular lesions in JLIS. Finally,
J AM ACAD DERMATOL
Re´my-Leroux et al 221
VOLUME 58, NUMBER 2
Fig 3. Histopathologic features of lupus erythematosus tumidus: mild epidermal atrophy and perivascular lymphocyte infiltration less dense as compared with Jessner’s lymphocytic infiltration of skin. (Hematoxylin-eosin stain; original magnification: 3100.)
Fig 5. Histopathologic features of Jessner’s lymphocytic infiltration of skin: dense perivascular lymphocyte infiltration. (Hematoxylin-eosin stain; original magnification: 3100.)
Fig 4. Histopathologic features of lupus erythematosus tumidus: mild thickening of dermoepidermal junction and focal vacuolization of basal keratinocytes. (Hematoxylineosin stain; original magnification: 3250.)
Fig 6. Histopathologic features of Jessner’s lymphocytic infiltration of skin: absence of epidermal and dermoepidermal junction abnormalities. (Hematoxylin-eosin stain; original magnification: 3250.)
histologic characteristics of the two groups obtained after histologic reclassification were compared again: only a slight epidermal atrophy was found more frequent in patients with LET (Table III).
reclassification, the extent to which JLIS and LET share numerous characteristics is striking, especially for age at onset, photosensitivity, response to antimalarial drugs, lack of extracutaneous involvement, and histologic findings (CD20 expression, presence of mucin). Interestingly, photosensitivity was most frequent at the beginning of the disease and disappeared over time, with progression occurring independently of photoexposure. According to Kuhn et al,17 the single presence of even slight epidermal or junctional histologic changes should exclude the tumid subset of LE. However, in a recent report by Vieira et al,16 minimal epidermal changes (atrophy, slight vacuolar degeneration of basal cells, slight to moderate hyperkeratosis and follicular plugging) were found in 18/26 LET cases and irregular basement membrane in 11/26. Similarly, Alexiades-Armenakas et al15 noticed focal dermoepidermal interface changes with vacuolar alterations and necrosis of keratinocytes in 3 of their 15 patients with LET. In our study, after
DISCUSSION The results of this study showed that JLIS and LET have more similarities than differences. Indeed, the differential diagnosis between them seems to rely on several particularities: clinical, ie, facial lesions, especially on the nose for women with LET, and annular lesions predominantly on the back for JLIS; and immunopathologic, ie, a positive lupus band test result for LET; none of which are specific. In our series, the rarity of high-titer antinuclear antibodies in either group, the absence of positive lupus band test results in JLIS, and their irregular positivity in LET are in accordance with the literature.2,3,13,16-18 After reclassification of patients based on blinded histologic review, the clinical differences were almost totally erased. However, before or after the
222 Re´my-Leroux et al
J AM ACAD DERMATOL FEBRUARY 2008
Table III. Comparison of patient characteristics after slide review and reclassification Diagnosis after histologic review
Patients, n Age at onset, means 6 SD, y F/M ratio No. of lesions, n (%) \5 [10 Location, n (%) Face Forehead Cheeks Temples Bridge of nose Back Neck, shoulders, and chest Hands Arms Other Type of lesion, n (%) Annular Plaques Papules Type of progression, n (%) Flares Photosensitivity Positive lupus band test result, n (%) Antinuclear antibodies, n (%) Epidermal atrophy Slight Marked Epidermal vacuolization Discontinuous Continuous Thickened DEJ Focal [2/3 of DEJ Lymphocyte-infiltrate location: Periadnexal (moderate or dense) Perivascular: Moderate Dense
JLIS
LET
P
11 18 29.9 6 6.7 34.4 6 6.7 NS 6/5
12/6
NS
2/10 (20) 5/10 (50)
8/17 (47) 9/17 (53)
NS NS
7/11 (64) 2/5 (40) 5/5 (100) 4/5 (80) 0/7 9/11 (82) 5/11 (45) 1/11 (9) 5/11 (45) 3/11 (27)
13/18 8/13 12/13 4/13 7/13 9/18 4/18 3/18 6/18 5/18
(72) (62) (92) (31) (54) (50) (22) (17) (33) (28)
NS NS NS NS .04 NS NS NS NS NS
6/11 (55) 3/18 (17) 2/11 (18) 9/18 (50) 7/11 (64) 10/18 (56)
.05 NS NS
10/11 (91) 17/18 (94) 11/11 (100) 14/18 (78) 0 1/14 (7)
NS NS NS
3/10 (30)
1/17 (6)
NS
1/11 (9) 0
7/18 (39) 0
.04 NS
4/11 (36) 0
8/18 (45) 6/18 (34)
NS NS
1/11 (9) 0
6/18 (33,5) NS 1/18 (5,5) NS
10/11 (91) 16/18 (89)
NS
11/11 (100) 18/18 (100) NS 2/11 (18) 11/18 (61) .05 9/11 (82) 7/18 (39)
DEJ, Dermopidermal junction; F, female; JLIS, Jessner’s lymphocytic infiltration of skin; LET, lupus erythematosus tumidus; M, male; NS, not significant.
histologic reclassification, only a slight epidermal atrophy histologic persisted as a potential histologic criterion for separating the two conditions. Thus, although a difference between two clinical pictures seems to have been accepted in the minds of
physicians, our findings support a broader but single histopathologiceclinical spectrum rather than two distinct entities. LET is considered a rare subtype of CCLE,14,16,19-21 which differs clinically from discoid subtype by the absence of follicular hyperkeratosis and scarring.15,22 Histologically, abundant interstitial mucin deposits have been reported in skin biopsy specimens from patients with LET,14-17 but not with JLIS.1 In our series, mucin deposits were detected in about 50% of the patients who were clinically given the diagnosis of either disease. Previous studies by Konttinen et al,23 Willemze et al,8 and Rijlaarsdam et al24 showed that the infiltrates in JLIS and CCLE were mainly composed of CD41 T cells whereas Cerio et al7 observed B and T lymphocytes in more than 50% of infiltrates of patients with JLIS (the remaining 50% had no Tcell component). Our data confirmed the presence of B lymphocytes in the dermal infiltrates of more than 50% of patients initially given the diagnosis of JLIS or LET. In both conditions, these CD201 cells were generally sparse and diffusely distributed, with a range of 2 to 30 positive cells per field (3250). The notion of photosensitivity in JLIS was raised early5,25 and was shown by Toonstra et al3 to occur in 24% of cases. More recently, Weber et al,26 described 10 cases of photo-induced JLIS, with appearance of the lesions delayed 3 to 6 days after exposure, with combined UVA and UVB triggering spectra for most patients, as confirmed further by our group.27 In addition, Kuhn et al28,29 showed that LET represents the most photosensitive subtype of lupus erythematosus. These findings and our current results confirm that both JLIS and LET belong to the spectrum of photodermatoses, although the association of sun exposure and lesions is sometimes neglected because of the long delay before their appearance. Phototesting may contribute to the differential diagnosis of other photodermatoses, such as polymorphous light eruption, but contribute nothing to the differential diagnosis between JLIS and LET. Because of the absence of strict relationship between their efficacy and the existence of photoinduction of the skin lesions, antimalarial drugs may be used as firstline therapy, even in the absence of photosensitivity, as we did for our 26 patients with JLIS or LET. Notably, thalidomide, the only treatment that has been evaluated in a randomized controlled trial in JLIS,30 was given to only 10 of our patients and never as first-line therapy. After a mean of 8 years of follow-up, no systemic involvement has been reported for any of our patients with JLIS or LET, as previously reported.14,16 Rare and debatable cases of LET that evolved toward systemic lupus have been reported, but always in
J AM ACAD DERMATOL
Re´my-Leroux et al 223
VOLUME 58, NUMBER 2
patients with simultaneous discoid lupus erythematosus12,13,15 whereas that association is not exceptional.10,12-14,21 The association of JLIS and discoid lupus erythematosus is more uncommon, probably because the presence of discoid-type lesions, in principle, excludes the diagnosis of JLIS.3,31 Indeed, the current study strongly favors the hypothesis of a continuous spectrum covering JLIS and LET, most of the cases corresponding to a predominantly or purely dermal form of CCLE.32 The authors wish to thank Drs Algros, Barneon, Cotten, Durlach, Lamant, Le Gall, Petrella, Picot, and Pinquier, and Prof Pluot for providing histopathologic slides; Drs Bonnevalle and Bouthors for their help in data collection; and Mrs J. Jacobson for editorial assistance. REFERENCES 1. Jessner M, Kanof NB. Lymphocytic infiltration of the skin. Arch Dermatol 1953;68:447-9. 2. Konttinen YT, Bergroth V, Johansson E, Nordstrom D, Malmstrom M. A long-term clinicopathologic survey of patients with Jessner’s lymphocytic infiltration of the skin. J Invest Dermatol 1987;89:205-8. 3. Toonstra J, Wildschut A, Boer J, Smeenk G, Willemze R, van der Putte SC, et al. Jessner’s lymphocytic infiltration of the skin: a clinical study of 100 patients. Arch Dermatol 1989;125:1525-30. 4. Toonstra J, van der Putte SC. Plasmacytoid monocytes in Jessner’s lymphocytic infiltration of the skin: a valuable clue for the diagnosis. Am J Dermatopathol 1991;13:321-8. 5. Gottlieb B, Winkelmann RK. Lymphocytic infiltration of the skin. Arch Dermatol 1962;86:626-33. 6. Calnan CD. Lymphocytic infiltration of the skin (Jessner). Br J Dermatol 1957;69:169-73. 7. Cerio R, Oliver GF, Jones EW, Winkelmann RK. The heterogeneity of Jessner’s lymphocytic infiltration of the skin: immunohistochemical studies suggesting one form of perivascular lymphocytoma. J Am Acad Dermatol 1990;23:63-7. 8. Willemze R, Vermeer BJ, Meijer CJ. Immunohistochemical studies in lymphocytic infiltration of the skin (Jessner) and discoid lupus erythematosus: a comparative study. J Am Acad Dermatol 1984;11:832-40. 9. Weyers W, Bonczkowitz M, Weyers I. LE or not LEethat is the question: an unsuccessful attempt to separate lymphocytic infiltration from the spectrum of discoid lupus erythematosus. Am J Dermatopathol 1998;20:225-32. 10. Dekle CL, Mannes KD, Davis LS, Sangueza OP. Lupus tumidus. J Am Acad Dermatol 1999;41:250-3. 11. Gougerot H, Burnier R. Lupus erythematodes ‘‘tumidus’’. Bull Soc Fr Dermatol Syph 1930;37:1291-2. 12. Ruiz H, Sanchez JL. Tumid lupus erythematosus. Am J Dermatopathol 1999;21:356-60. 13. Choonhakarn C, Poonsriaram A, Chaivoramukul J. Lupus erythematosus tumidus. Int J Dermatol 2004;43:815-8. 14. Kuhn A, Richter-Hintz D, Oslislo C, Ruzicka T, Megahed M, Lehmann P. Lupus erythematosus tumidusea neglected subset of cutaneous lupus erythematosus: report of 40 cases. Arch Dermatol 2000;136:1033-41.
15. Alexiades-Armenakas MR, Baldassano M, Bince B, Werth V, Bystryn JC, Kamino H, et al. Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis. Arthritis Rheum 2003;49:494-500. 16. Vieira V, Del Pozo J, Yebra-Pimentel MT, Martinez W, Fonseca E. Lupus erythematosus tumidus: a series of 26 cases. Int J Dermatol 2006;45:512-7. 17. Kuhn A, Sonntag M, Ruzicka T, Lehmann P, Megahed M. Histopathologic findings in lupus erythematosus tumidus: review of 80 patients. J Am Acad Dermatol 2003;48:901-8. 18. Ten Have-Opbroek AAW. On the differential diagnosis between chronic discoid lupus erythematodes and lymphocytic infiltration of the skin (Jessner), with emphasis on fluorescence microscopy. Dermatologica 1966;132:109-14. 19. Gougerot H, Burnier R. Lupus e´rythe´mateux tumidus. Bull Soc Fr Dermatol Syph 1931;38:195. 20. Gougerot H, Carteaud A. Lupus e´rythe´mateux tumidus. Bull Soc Fr Dermatol Syph 1931;38:195-6. 21. Casala AM, Bianchi C, Bianchi O, Stringa SG. Lupus e´rythe´mateux tumidus (lymphocytic infiltration of the skin) et lupus e´rythe´mateux chronique associe´s chez le meˆme malade. Etude immunofluorescente. Bull Soc Fr Dermatol Syph 1971;78: 256-8. 22. France`s C, Barete S, Ayoub N, Piette J. Classification des le´sions dermatologiques du lupus. Ann Med Interne (Paris) 2003; 154:33-44. 23. Konttinen YT, Reitamo S, Ranki A, Segerberg-Konttinen M. T lymphocytes and mononuclear phagocytes in the skin infiltrate of systemic and discoid lupus erythematosus and Jessner’s lymphocytic infiltrate. Br J Dermatol 1981;104:141-5. 24. Rijlaarsdam JU, Nieboer C, De Vries E, Willemze R. Characterization of the dermal infiltrates in Jessner’s lymphocytic infiltrate of the skin, polymorphous light eruption and cutaneous lupus erythematosus: differential diagnostic and pathogenetic aspects. J Cutan Pathol 1990;17:2-8. 25. Krieger BL. Lymphocytic infiltration of the skin (Jessner). Arch Dermatol 1969;100:247-8. 26. Weber F, Schmuth M, Fritsch P, Sepp N. Lymphocytic infiltration of the skin is a photosensitive variant of lupus erythematosus: evidence by phototesting. Br J Dermatol 2001; 144:292-6. 27. Adamski H, Labrousse AL, Sparsa A, Leonard F, Le Gall F, Labrousse F, et al. Photode´clenchement des le´sions dans la maladie de Jessner-Kanof. Ann Dermatol Venereol 2002;129:1370-3. 28. Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, Megahed M, Ruzicka T, et al. Phototesting in lupus erythematosus: a 15year experience. J Am Acad Dermatol 2001;45:86-95. 29. Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, Megahed M, Ruzicka T, et al. Phototesting in lupus erythematosus tumidusereview of 60 patients. Photochem Photobiol 2001;73:532-6. 30. Guillaume JC, Moulin G, Dieng MT, Poli F, Morel P, Souteyrand P, et al. Crossover study of thalidomide vs placebo in Jessner’s lymphocytic infiltration of the skin. Arch Dermatol 1995; 131:1032-5. 31. Lipsker D, Mitschler A, Grosshans E, Cribier B. Could Jessner’s lymphocytic infiltrate of the skin be a dermal variant of lupus erythematosus? An analysis of 210 cases. Dermatology 2006;213:15-22. 32. Lipsker D. Classification of specific cutaneous manifestations in patients with lupus erythematosus: a time for change? Dermatology 2006;212:324-6.